{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:25:28Z","timestamp":1787192728191,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neurodevelopmental disorder with spasticity, epilepsy and brain atrophy (NEDESBA) is a rare autosomal recessive condition, first described in 2020. It has been associated with biallelic pathogenic variants in the Trafficking Protein Particle Complex Subunit 4 (TRAPPC4) gene. This disorder belongs to the expanding group of TRAPPopathies, caused by mutations in genes encoding components of the transport protein particle (TRAPP) complex, which are essential for intracellular trafficking, autophagy and dendritic spine morphogenesis. Variants in these genes typically result in overlapping clinical features, including microcephaly, early\u2010onset epilepsy, intellectual disability, neurodevelopmental regression, spasticity and abnormal brain MRI findings. Here, we report a 13\u2010month\u2010old affected male born to consanguineous parents, presenting with epileptic spasms and progressive neurodevelopmental delay. Importantly, proband also exhibits hair loss and skin rashes in early infancy. Initial metabolic screening suggested biotinidase deficiency, based on low biotin levels (0.6\u2009nmol\/min\/mL; normal\u2009&gt;\u20095) and overlapping clinical symptoms. However, confirmatory biochemical and enzymatic studies ruled out classic biotinidase deficiency. Whole exome sequencing revealed a homozygous splice\u2010site variant (c.454+3A&gt;G) in the TRAPPC4 gene, confirming the diagnosis of NEDESBA. This variant has been reported in multiple previous reports, mainly born out of consanguineous marriages. The phenotypic overlap between metabolic and genetic neurodevelopmental disorders in these cases emphasizes the critical role of early molecular testing in achieving a precise diagnosis.<\/jats:p>","DOI":"10.1002\/jdn.70167","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:16:03Z","timestamp":1785737763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Case Report and a Review of TRAPPC4\u2010Related TRAPPopathy"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9174-7342","authenticated-orcid":false,"given":"Anil","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Human Genetics and Molecular Medicine Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Molecular Medicine Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvinder","family":"Wander","sequence":"additional","affiliation":[{"name":"Department of Pediatrics All India Institute of Medical Sciences  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-8592","authenticated-orcid":false,"given":"Anjana","family":"Munshi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Molecular Medicine Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.26650\/jchild.2023.1294229"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14557"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","unstructured":"Forno A. J.Oliveira M. Z.Amorim C.Concei\u00e7\u00e3o andP. R.Sousa.2025. \u201cChild Neurology: TRAPPC4\u2010Related Neurodevelopmental Disorder.\u201d104 no.9:e213538.","DOI":"10.1212\/WNL.0000000000213538"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-00717-5"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252413329"},{"issue":"4","key":"e_1_2_12_7_1","article-title":"Recurrent Bi\u2010Allelic Splicing Variant c. 454+ 3A> G in TRAPPC4 Is Associated With Progressive Encephalopathy and Muscle Involvement","volume":"143","author":"Kaur P.","year":"2020","journal-title":"Brain"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00020"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","unstructured":"Kummel D. U.Heinemann andP.Science.2008. \u201cDiversity in Structure and Function of Tethering Complexes: Evidence for Different Mechanisms in Vesicular Transport Regulation.\u201d9 no.2:197\u2013209.","DOI":"10.2174\/138920308783955252"},{"issue":"01","key":"e_1_2_12_10_1","article-title":"Neurodegenerative Disease Caused by the TRAPPC4 Gene","volume":"81","author":"Lima A. F.","year":"2023","journal-title":"Arquivos de Neuro\u2010Psiquiatria"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12452"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.aian_1108_21"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa256"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz374"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020408"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jdn.70167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jdn.70167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jdn.70167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:12:15Z","timestamp":1787191935000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jdn.70167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jdn.70167"],"URL":"https:\/\/doi.org\/10.1002\/jdn.70167","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"value":"0736-5748","type":"print"},{"value":"1873-474X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70167"}}